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Exercise is shown to improve cognitive function in various human and animal studies. Laboratory mice are often used as a model to study the effects of physical activity and running wheels provide a voluntary and non-stressful form of exercise. The aim of the study was to analyze whether the cognitive state of a mouse is related to its wheel-running behavior. Twenty-two male C57BL/6NCrl mice (9.5 weeks old) were used in the study. The cognitive function of group-housed mice (n = 5–6/group) was first analyzed in the IntelliCage system followed by individual phenotyping with the PhenoMaster with access to a voluntary running wheel. The mice were divided into three groups according to their running wheel activity: low, average, and high runners. The learning trials in the IntelliCage showed that the high-runner mice exhibited a higher error rate at the beginning of learning trials but improved their outcome and learning performance more compared to the other groups. The high-runner mice ate more compared to the other groups in the PhenoMaster analyses. There were no differences in the corticosterone levels between the groups, indicating similar stress responses. Our results demonstrate that high-runner mice exhibit enhanced learning capabilities prior to access to voluntary running wheels. In addition, our results also show that individual mice react differently when introduced to running wheels, which should be taken into consideration when choosing animals for voluntary endurance exercise studies.

Cardiovascular disease (CVD) causes a high disease burden. Physical activity (PA) reduces CVD morbidity and mortality. We aimed to determine the relationship between the composition of moderate-to-vigorous PA (MVPA), light PA (LPA), sedentary behavior (SB), and sleep during midlife to the incidence of major adverse cardiac events (MACE) and all-cause mortality at a 7-year follow-up. The study population consisted of Northern Finland Birth Cohort 1966 members who participated in the 46-year follow-up in 2012 and were free of MACE (N = 4147). Time spent in MVPA, LPA, and SB was determined from accelerometer data. Sleep time was self-reported. Hospital visits and deaths were obtained from national registers. Participants were followed until December 31, 2019, or first MACE occurrence (acute myocardial infarction, unstable angina pectoris, stroke, hospitalization due to heart failure, or death due to CVD), death from another cause, or censoring. Cox proportional hazards model was used to estimate hazard ratios of MACE incidence and all-cause mortality. Isotemporal time reallocations were used to demonstrate the dose–response association between time spent in behaviors and outcome. The 24-h time composition was significantly associated with incident MACE and all-cause mortality. More time in MVPA relative to other behaviors was associated with a lower risk of events. Isotemporal time reallocations indicated that the greatest risk reduction occurred when MVPA replaced sleep. Higher MVPA associates with a reduced risk of incident MACE and all-cause mortality after accounting for the 24-h movement composition and confounders. Regular engagement in MVPA should be encouraged in midlife.

Background: All coronary artery disease (CAD) patients do not benefit equally of secondary prevention. Individualized intensity of drug therapy is currently implemented in guidelines for CAD and diabetes. Novel biomarkers are needed to identify patient subgroups potentially benefitting from individual therapy. This study aimed to investigate endothelin-1 (ET-1) as a biomarker for increased risk of adverse events and to evaluate if medication could alleviate the risks in patients with high ET-1. Methods: A prospective observational cohort study ARTEMIS included 1946 patients with angiographically documented CAD. Blood samples and baseline data were collected at enrollment and the patients were followed for 11 years. Multivariable Cox regression was used to assess the association between circulating ET-1 level and all-cause mortality, cardiovascular (CV) death, non-CV death and sudden cardiac death (SCD). Results: Here we show an association of circulating ET-1 level with higher risk for all-cause mortality (HR: 2.06; 95% CI 1.5–2.83), CV death, non-CV death and SCD in patients with CAD. Importantly, high intensity statin therapy reduces the risk for all-cause mortality (adjusted HR: 0.05; 95% CI 0.01–0.38) and CV death (adjusted HR: 0.06; 95% CI 0.01–0.44) in patients with high ET-1, but not in patients with low ET-1. High intensity statin therapy does not associate with reduction of risk for non-CV death or SCD. Conclusions: Our data suggests a prognostic value for high circulating ET-1 in patients with stable CAD. High intensity statin therapy associates with reduction of risk for all-cause mortality and CV death in CAD patients with high ET-1.

Background: Health care budgets are limited, requiring the optimal use of resources. Machine learning (ML) methods may have an enormous potential for effective use of health care resources. Objective: We assessed the applicability of selected ML tools to evaluate the contribution of known risk markers for prognosis of coronary artery disease to predict health care costs for all reasons in patients with a recent acute coronary syndrome (n = 65, aged 65 ± 9 years) for 1-year follow-up. Methods: Risk markers were assessed at baseline, and health care costs were collected from electronic health registries. The Cross-decomposition algorithms were used to rank the considered risk markers based on their impacts on variances. Then regression analysis was performed to predict costs by entering the first top-ranking risk marker and adding the next-best markers, one by one, to build up altogether 13 predictive models. Results: The average annual health care costs were €2601 ± €5378 per patient. The Depression Scale showed the highest predictive value (r = 0.395), accounting for 16% of the costs (P = .001). When the next 2 ranked markers (LDL cholesterol, r = 0.230; and left ventricular ejection fraction, r = -0.227, respectively) were added to the model, the predictive value was 24% for the costs (P = .001). Conclusion: Higher depression score is the primary variable forecasting health care costs in 1-year follow-up among acute coronary syndrome patients. The ML tools may help decision-making when planning optimal utilization of treatment strategies.

Background: Effective treatment and prevention of cardiovascular (CV) diseases requires reliable methods of assessing individual CV event risk. Although standardized risk calculators like Systematic Coronary Risk Evaluation (SCORE) are sufficient in most instances, sometimes more specific clinical examination is needed to determine the most optimal intervention and its intensity. Aim: To study whether carotid and femoral bruits provide prognostic information on CV events, CV mortality and all-cause mortality beyond traditional CV risk factors. Methods: 1045 subjects (49.8% men), aged 51.3 ± 5.97 years were clinically examined in the beginning of 1990’s. The subjects were followed for over 20 years and data on CV events and causes of deaths was collected. Results: During the follow-up period, 241 (23.1%) of the subjects died and 82 (34.6%) of the deaths were of CV origin. Carotid bruits were a significant risk factor for CV deaths only if subjects with previous CV events were included. After adjusting for age, sex, systolic blood pressure, smoking, diabetes, LDL cholesterol, coronary artery disease and stroke, carotid bruits posed a hazard ratio (HR) (95% confidence interval) of 4.15 (2.39–8.52) p<0.001 for CV deaths. After excluding subjects with previous CV events (after which n = 941) neither carotid nor femoral bruits were statistically associated with CV events or all-cause mortality. Adding carotid or femoral bruits in the baseline risk model with traditional CV risk factors did not improve C-statistic, reclassification, or discrimination of the subjects. Conclusions: Carotid and femoral bruits do not provide clinically useful information in a pure primary prevention setting. Carotid bruits might be useful in evaluating the overall CV risk in a population where recurrent CV events may occur.

Objectives: To investigate whether an earlier-onset climacteric phase is associated with autonomic imbalance at the age of 46 years. Methods: This cross-sectional birth cohort study included 2661 women aged 46 years. Participants were divided into climacteric (n = 359) and preclimacteric (n = 2302) groups based on menstrual history and follicle stimulating hormone values. The mean heart rate (HR), low-frequency (LF) power, high-frequency (HF) power and LF/HF ratio were analyzed from heart rate variability recordings. The variables were compared between the groups using multivariable linear regression models, including body mass index, smoking and physical activity. The effects of hormone therapy and hot flashes on autonomic function were evaluated in sub-analyses. Results: Climacteric women had a lower mean HR in seated (71.9 ± 10.5 vs. 72.6 ± 10.4 bpm, p = 0.015) and standing (81.2 ± 12.8 vs. 83.6 ± 12.1 bpm, p = 0.002) positions compared to preclimacteric women, and the differences remained significant after the adjustments. In the sub-analyses, more frequent hot flashes were associated with a lower LF power and LF/HF ratio in the sitting position. Conclusions: The present study suggested an association between greater parasympathetic activation in women with more advanced climacteric status at the age of 46 years.

Our aim was to compare three research-grade accelerometers for their accuracy in step detection and energy expenditure (EE) estimation in a laboratory setting, at different speeds, especially in overweight/obese participants. Forty-eight overweight/obese subjects participated. Participants performed an exercise routine on a treadmill with six different speeds (1.5, 3, 4.5, 6, 7.5, and 9 km/h) for 4 min each. The exercise was recorded on video and subjects wore three accelerometers during the exercise: Sartorio Xelometer (SX, hip), activPAL (AP, thigh), and ActiGraph GT3X (AG, hip), and energy expenditure (EE) was estimated using indirect calorimetry for comparisons. For step detection, speed-wise mean absolute percentage errors for the SX ranged between 9.73–2.26, 6.39–0.95 for the AP, and 88.69–2.63 for the AG. The activPALs step detection was the most accurate. For EE estimation, the ranges were 21.41–15.15 for the SX, 57.38–12.36 for the AP, and 59.45–28.92 for the AG. All EE estimation errors were due to underestimation. All three devices were accurate in detecting steps when speed exceeded 4 km/h and inaccurate in EE estimation regardless of speed. Our results will guide users to recognize the differences, weaknesses, and strengths of the accelerometer devices and their algorithms.

Objective: We propose a non-contact approach for atrial fibrillation (AF) detection from face videos. Methods: Our proposed method can accurately extract systolic peaks from face videos for AF detection. The proposed method is trained with subject-independent 10-fold cross-validation with 30s video clips and tested on two tasks. 1) Classification of healthy versus AF: the accuracy, sensitivity, and specificity are 96.00%, 95.36%, and 96.12%. 2) Classification of SR versus AF: the accuracy, sensitivity, and specificity are 95.23%, 98.53%, and 91.12%. In addition, we also demonstrate the feasibility of non-contact AFL detection. Conclusion: We achieve good performance of non-contact AF detection by learning systolic peaks. Significance: non-contact AF detection can be used for self-screening of AF symptoms for suspectable populations at home or self-monitoring of AF recurrence after treatment for chronic patients.

Background and aims: Both carotid intima-media thickness (IMT) and arterial plaques have been shown to predict future CV events. Since there are no previous studies on the subject, our objective was to compare carotid IMT and the length of plaques in abdominal-pelvic main arteries in CV risk assessment in a prospective study setting with a follow-up of over 20 years. Methods: A total of 1007 patients (50% men), aged 51 ± 6.0 years, participated in the current study. Carotid IMT and the summarized plaque length (SUM) from abdominal aorta to common femoral arteries were ultrasonographically assessed. Patients were followed-up a median (1st-3rd quartile) of 22.5 (17.5–23.2) years for CV events. Results: SUM significantly predicted CV events (HR per every 10 mm increase: 1.035, 95% CI: 1.027–1.044, p < 0.001). Those in the highest SUM tertile had over 3-fold risk for CV event (HR: 3.392, 95% CI: 2.427–4.741, p < 0.001) when compared to those in the lowest tertile. SUM significantly predicted CV events even after adjusting for age, sex, hypertension, diabetes, smoking (pack-years), LDL cholesterol and IMT. Adding SUM to the established model improved C-index (95% CI) from 0.706 (0.674–0.738) to 0.718 (0.688–0.747) as well as both discrimination (p < 0.001) and reclassification (p < 0.001) of the patients. In contrast, IMT predicted cardiovascular events only in univariate analysis and it did not improve discrimination or reclassification of the patients. Conclusions: In light of our findings, SUM is a superior indicator and clinical tool for evaluating the overall CV risk compared to carotid IMT.

Cardiovascular (CV) diseases are the number one cause of mortality worldwide, causing nearly 19 million deaths in 2019. Estimating the individual CV risk is essential for targeting the preventative interventions more effectively. Currently, international guidelines recommend using standardized risk calculators for estimating the patient’s future risk of a CV event. In “borderline” risk individuals, these guidelines further recommend using additional clinical tests, such as coronary artery calcium score, for refining the risk estimation and guiding the clinical treatment decisions. Relatively little is known about much simpler and safer clinical tests in CV risk assessment. The aim of the current study was to explore whether plasma resistin concentration, carotid or femoral bruits, or ultrasonographically assessed carotid intima-media thickness (IMT) and abdominal aorta plaques could provide additional prognostic information beyond traditional CV risk factors in individual risk assessment. The study population consisted of middle-aged and elderly Finnish subjects participating in the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) project. Our results show that increasing plasma resistin concentration is associated with significantly increased risk of all-cause mortality in elderly Finnish participants. Similarly, our results show that an audible bruit from either carotid or femoral arteries is a strong predictor of fatal CV events in a middle-aged population. Ultrasonographically assessed carotid IMT is a controversial surrogate marker of subclinical atherosclerosis, and our results indicate that it does not predict CV events after adjusting for other CV risk factors. On the other hand, our results show that ultrasonographically measured abdominal aorta plaque length is a strong predictor of future CV events and provides prognostic information in addition to traditional CV risk factors during a follow-up period of over 20 years. In conclusion, this, Tiivistelmä Sydän- ja verisuonisairaudet (SV) ovat maailman yleisin kuolleisuuden syy aiheuttaen lähes 19 miljoonaa kuolemaa vuonna 2019. Yksilöllinen SV-sairauksien riskinarvio on ensiarvoisen tärkeää ennaltaehkäisevien toimenpiteiden tehokkaassa kohdentamisessa. Kansainväliset suositukset suosittelevat riskilaskureiden käyttöä potilaan tulevan SV-tapahtuman riskinarviossa. Samat suositukset kehottavat käyttämään tarkentavia kliinisiä tutkimuksia, kuten sepelvaltimoiden kalsifikaatioiden pisteytystä, riskinarvion ja kliinisten hoitopäätösten tukena yksilöillä, joiden SV-tapahtuman riski on ”rajaviivalla”. Verrattain vähän tiedetään paljon yksinkertaisemmista kliinisistä testeistä SV-tapahtumien riskinarviossa. Tämän tutkimuksen tarkoitus oli selvittää tuovatko plasman resistiinipitoisuus, kaula- tai reisivaltimosta kuullut suhinat tai ultraäänellä määritetty kaulavaltimon intima-media paksuus (IMT) ja vatsa-aortan plakkien pituus prognostista informaatiota tavanomaisten SV-sairauksien riskitekijöiden lisäksi yksilöllisessä riskinarviossa. Tutkimuksen aineisto koostuu keski-ikäisistä ja iäkkäistä suomalaisista, jotka osallistuivat Oulu Project Elucidating Risk of Atherosclerosis (OPERA) -projektiin. Tuloksemme osoittavat, että kohonnut plasman resistiinipitoisuus on yhteydessä merkittävästi kohonneeseen kuolleisuuteen iäkkäillä henkilöillä. Vastaavasti tuloksemme osoittavat, että joko kaula- tai reisivaltimosta auskultoiden kuultu suhina on voimakas fataalien SV-tapahtumien ennustaja keski-ikäisillä henkilöillä. Ultraäänellä määritetty kaulavaltimon IMT on kiistanalainen subkliinisen ateroskleroosin mitta, ja tuloksemme näyttivät, ettei se ennustanut tulevia SV-tapahtumia, kun riskimalli vakioitiin tavanomaisilla riskitekijöillä. Sen sijaan tuloksemme näyttivät, että ultraäänellä määritetty vatsa-aortan plakkien pituus on voimakas tulevien SV-tapahtumien ennustaja ja plakkien pituus antaa prognostista informaatiota tavanomaisten SV-riskitekijöiden lisäksi yli 20 vuo

Physical activity (PA) is one of the most efficient ways to prevent obesity and its associated diseases worldwide. In the USA, less than 10% of the adult population were able to meet the PA recommendations when accelerometers were used to assess PA habituation. Accelerometers significantly differ from each other in step recognition and do not reveal raw data. The aim of our study was to compare a novel accelerometer, Sartorio Xelometer, which enables to gather raw data, with existing accelerometers ActiGraph GT3X+ and activPAL in terms of step detection and energy expenditure estimation accuracy. 53 healthy subjects were divided into 2 cohorts (cohort 1 optimization; cohort 2 validation) and wore 3 accelerometers and performed an exercise routine consisting of the following speeds: 1.5, 3, 4.5, 9 and 10.5 km/h (6 km/h for 2nd cohort included). Data from optimization cohort was used to optimize Sartorio step detection algorithm. Actual taken steps were recorded with a video camera and energy expenditure (EE) was measured. To observe the similarity between video and accelerometer step counts, paired samples t test and intraclass correlation were used separately for step counts in different speeds and for total counts as well as EE estimations. In speeds of 1.5, 3, 4.5, 6, 9 and 10.5 km/h mean absolute percentage error (MAPE) % were 8.1, 3.5, 4.3, 4.2, 3.1 and 7.8 for the Xelometer, respectively (after optimization). For ActiGraph GT3X+ the MAPE-% were 96.93 (87.4), 34.69 (23.1), 2.13 (2.3), 1.96 (2.6) and 2.99 (3.8), respectively and for activPAL 6.55 (5.6), 1.59 (0.6), 0.81 (1.1), 10.60 (10.3) and 15.76 (13.8), respectively. Significant intraclass correlations were observed with Xelometer estimates and actual steps in all speeds. Xelometer estimated the EE with a MAPE-% of 30.3, activPAL and ActiGraph GT3X+ with MAPE percentages of 20.5 and 24.3, respectively. The Xelometer is a valid device for assessing step counts at different gait speeds. MAPE is differe

Objective: Resistin is a small, cysteine-rich proinflammatory molecule that is primarily secreted by peripheral blood mononuclear cells and macrophages in humans. Previous studies have shown resistin to participate in various pathological processes including atherosclerosis and cancer progression but not many studies have assessed the role of resistin as a risk factor for all-cause mortality. The objective of this prospective study was to evaluate whether resistin predicts mortality among elderly Finnish people. Methods: The study population consisted of 599 elderly (71.7 ± 5.4 years) patients and the follow-up was approximately six years. A thorough clinical examination including anthropometric and other clinical measurements such as blood pressure as well as various laboratory parameters (including resistin) was conducted at baseline. Results: After the follow-up, 65 (11%) of the patients died. Resistin was a significant risk factor for all-cause mortality (HR 3.02, 95% CI: 1.64–5.56, p<0.001) when the highest tertile was compared to the lowest. Resistin remained as a significant risk factor even after adjusting for various covariates such as age, sex, systolic blood pressure, smoking habits, alcohol consumption, medications (antihypertensive, lipid-lowering, glucose-lowering), hsCRP and leisure time physical activity. Receiver operating characteristic (ROC) curve analysis for resistin demonstrated area under the curve (AUC) of 0.656 (95% CI: 0.577–0.734), p<0.001 and an optimal cutoff value of 12.88 ng/ml. Conclusions: Our results indicate that resistin is a significant risk factor for all-cause mortality among elderly Finnish subjects, independent from traditional cardiovascular risk factors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. Method: we investigated a large cohort of 608 subjects, born in 1945 in Oulu, Finland (Oulu Cohort 1945). We studied the effects of PSCK9 lev-els with different glucose tolerances (normal glucose tolerance (NGT), prediabetes (PreDM) or type 2 diabetes (T2D)) with and without statin medication, and analyzed clinical data, NMR metabolomics and PCSK9 plasma levels. Results: PCSK9 plasma levels did not significantly differ between the three groups. Statin therapy significantly increased the PCSK9 levels in NGT, PreDM and T2D groups compared with subjects with no statins. In the NGT group, negative associations between PCSK9 and LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol and LDL and IDL triglycerides were observed under statin medication. In contrast, in the PreDM and T2D groups, these associa-tions were lost. Conclusions: our data suggest that in subjects with abnormal glucose metabolism and statin therapy, the significant PCSK9-mediated effects on the lipid metabolites are lost com-pared to NGT subjects, but statins reduced the LDL-C and VLDL-C levels.

There is increasing evidence suggesting that cardiovascular diseases have an early origin, already beginning during fetal life and in childhood. The autonomic nervous system plays an important role in the pathophysiology of various cardiovascular manifestations and cardiac left ventricular structure is related to cardiovascular morbidity and mortality in adulthood. The aim of this thesis was to investigate associations between fetal and childhood growth and cardiovascular autonomic regulation as well as cardiac structure and function in a middle-aged general population. This thesis also aimed to examine the association between life course physical activity and cardiovascular autonomic regulation in midlife. The study population was based on the prospective population-based Northern Finland 1966 Birth Cohort. This cohort has been followed from early gestation and frequent anthropometric measurements have been taken of the participants in infancy and childhood. At 46 years of age, 5861 participants underwent a comprehensive cardiometabolic examination, including an analysis of heart rate variability (n=5679), and in a subsample also an analysis of baroreflex sensitivity (n=2726) and an echocardiographic examination (n=1155). The results revealed that a higher birth weight in males was related to reduced vagal regulation of heart rate in midlife, but birth weight did not have a substantial association with cardiac left ventricular structure or function in midlife. Early growth patterns, particularly earlier adiposity rebound and higher body mass index at adiposity peak and at adiposity rebound, were associated with reduced cardiovascular vagal regulation and modifications in cardiac structure in midlife. A high level of life course physical activity was independently related to increased cardiovascular vagal regulation in females in midlife, while in males this association was mediated by other lifestyle and health related factors. In conclusion, this study in, Tiivistelmä Lisääntyvä näyttö viittaa sydän- ja verisuonisairauksien varhaiseen alkuperään jo ennen syntymää ja lapsuudessa. Sydämen autonomisella säätelyllä on tärkeä rooli erilaisten sydän- ja verisuonisairauksien ilmenemismuotojen patofysiologiassa ja sydämen vasemman kammion rakenne liittyy sydän- ja verisuonsairastavuuteen ja -kuolleisuuteen aikuisuudessa. Tämän väitöskirjatyön tarkoituksena oli selvittää sikiö- ja lapsuusajan kasvun yhteyttä sydämen autonomiseen säätelyyn, rakenteeseen ja toimintaan keski-ikäisessä väestössä. Väitöskirjatyön tarkoituksena oli myös tutkia elinikäisen fyysisen aktiivisuuden ja keski-ikäisen sydämen autonomisen säätelyn välistä yhteyttä. Tutkimuspopulaatio pohjautui Pohjois-Suomen syntymäkohorttiin 1966. Kohortin jäsenistä on tietoa alkuraskaudesta lähtien ja heistä on otettu toistuvia antropometrisia mittauksia imeväisiässä sekä lapsuudessa. 46-vuotiaana 5861 kohortin jäsentä osallistui kattavaan kardiometaboliseen kokonaisarvioon, johon sisältyi sykevaihtelun mittaus (n=5679) sekä osalla myös baroheijasteherkkyyden mittaus (n=2726) ja sydämen ultraäänitutkimus (n=1155). Tutkimuksessa havaittiin, että miehillä suurempi syntymäpaino liittyi heikentyneeseen sydämen autonomiseen säätelyyn keski-iässä, mutta syntymäpainolla ei ollut olennaista yhteyttä sydämen vasemman kammion rakenteeseen tai toimintaan keski-iässä. Varhaislapsuuden kasvu, etenkin lapsuuden painoindeksin varhainen kääntyminen nousuun sekä korkeampi painoindeksi imeväisiässä ja lapsuudessa, liittyivät heikentyneeseen sydämen autonomiseen säätelyyn sekä sydämen rakenteellisiin muutoksiin keski-iässä. Korkea elinikäinen fyysinen aktiivisuus liittyi itsenäisesti suotuisampaan sydämen autonomiseen säätelyyn keski-ikäisillä naisilla, kun taas miehillä tämä yhteys ei ollut riippumaton muista elämäntapaan ja terveyteen liittyvistä tekijöistä. Tutkimuksen tulokset osoittavat, että varhainen kasvu on yhteydessä sydämen autonomiseen säätelyyn ja rakenteeseen keski-ikäisessä v

Background: Fragmented QRS (fQRS) on 12-lead electrocardiogram (ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. Methods: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 ± 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of ≥50% (70% men; 66.6 ± 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 ± 8.5 yrs). Results: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p < 0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p < 0.001), CAD patients without prior MI (39.9% vs. 26.4%, p < 0.001), CAD patients with prior MI (42.9% vs. 31.2%, p < 0.001), and victims of SCD (56.4% vs. 44.4%, p < 0.001). Conclusions: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men.

Objective: To evaluate cardiac autonomic function in adults born preterm. Study design: We studied the association between prematurity and cardiac autonomic function using heart rate variability measurements in 600 adults (mean age of 23.3 years) from a geographically based cohort in Northern Finland. There were 117 young adults born early preterm (<34 weeks), 207 born late preterm (34–36 weeks), and 276 born at term (≥37 weeks, controls). Autonomic function was analyzed by calculating time and frequency domain heart rate variability measurements using linear regression. Results: Compared with controls, the mean difference in root mean square of successive differences (indicating cardiac vagal activity) was −12.0% (95% CI −22.2%, −0.5%, adjusted for sex, age, source cohort, and season P = .04) for the early preterm group and −7.8% (−16.8%, 2.0%, P = .12) for the late preterm group. Mean differences with controls in low frequency power (indicating cardiac vagal activity, including some sympathetic- and baroreflex-mediated effects) were −13.6% (−26.7%, 1.8%, P = .08) for the early preterm group and −16.4% (−27.0%, −4.3%, P = .01) for the late preterm group. Mean differences in high frequency power (quantifying cardiac vagal modulation in respiratory frequency) were −19.2% (−36.6%, 2.9%, P = .09) for the early preterm group and −13.8% (−29.4%, 5.3%, P = .15) for the late preterm group. Differences were attenuated when controlled for body mass index and physical activity. Conclusions: Our results suggest altered autonomic regulatory control in adults born preterm, including those born late preterm. Altered autonomic regulatory control may contribute to increased cardiovascular risk in adults born preterm.

Background: Heart rate variability (HRV) and baroreflex sensitivity (BRS) measurements provide means for the objective assessment of cardiovascular autonomic function. As previous studies have associated chronic pain with abnormal autonomic function, we aimed to characterize the relationship between the number of musculoskeletal pain sites (NPS), pain intensity, and cardiovascular autonomic function among the population-based Northern Finland Birth Cohort 1966. Methods: At the age of 46, cohort members self-reported their musculoskeletal pains (enabling the determination of NPS [0–8] and pain intensity [Numerical Rating Scale, NRS, 0–10]) and underwent clinical assessments of cardiovascular autonomic function in seated and standing positions (HRV variables: heart rate [HR] and root mean square of successive differences in beat-to-beat intervals [rMSSD] for the entire cohort; BRS variables: low-frequency systolic blood pressure variability [SBPV] and cross-spectral baroreflex sensitivity [BRS] for those attending the examination in Oulu, Finland). Extensive confounder data were also collected (body mass index, physical activity, smoking, Hopkins Symptom Checklist-25, comorbidities, and medications). The full samples included 4186 and 2031 individuals (HRV and BRS samples, respectively). Three subanalyses focused on individuals with intense and frequent pain, individuals with symptoms of depression and anxiety, and the relationship between pain intensity and autonomic parameters. Results: Linear regression models showed varying associations between NPS, pain intensity, and cardiovascular autonomic parameters. However, after all adjustments NPS was only associated with one outcome among women (BRS, standing: beta = − 0.015, p = 0.048) and two among men (HR, seated: beta = − 0.902, p = 0.003; HR, standing: beta = − 0.843, p = 0.014). Pain intensity was not associated with any outcome after full adjustments. Significant sex*pain interactions were found in the da

A cardiorespiratory system is highly regulated via the autonomic nervous system (ANS), whose function can be quantified noninvasively by analyzing electrocardiogram (ECG), blood pressure (BP) and respiration signals. Several conditions and illnesses are linked with imbalance of the ANS. This thesis aimed to develop methods for describing the ANS regulation of a cardiovascular system from short-term cardiorespiratory measurements. More specifically, the role of breathing rate and its effects on traditional frequency domain based cardiovascular indexes describing ANS control is addressed. The main contributions are as follows: 1) an adaptive filtering based method to remove respiratory influences from cardiovascular signals and indexes was developed. The adaptive filter reduced the bias caused by low respiration rate, enabling the usage of spontaneous respiration measurement protocol over controlled respiration. 2) Methods to quantify respiratory sinus arrhythmia (RSA) index from cardiovascular signals were developed as well: two methods utilizes adaptive filtering and either the measured respiration signal or the ECG-derived respiration signal and one method uses independent component analysis. Developed RSA index methods allow varying respiration rates making them physiologically more accurate than traditional high frequency power with fixed respiration rate, often used as RSA index. 3) Tools for studying the power and the frequency of low frequency (LF) oscillations of cardiovascular signals were developed, including a time-frequency representation for analyzing varying data. An experimental study was conducted with patients of continuum of cardiovascular risks. According to results, aging decreased the frequency of LF oscillation, whereas coronary artery disease decreased it further. 4) Two new ECG-derived respiration (EDR) methods utilizing decomposition techniques were developed. The proposed methods yielded statistically significant improvements over p, Tiivistelmä Autonominen hermosto säätelee tarkasti sydän- ja verenkiertoelimistöä sekä hengitystä. Autonomisen hermoston toimintaa voidaan analysoida laskennallisin menetelmin noninvasiivisesti mitatuista elektrokardiogrammi- (EKG, sydänsähkökäyrä), verenpaine- ja hengityssignaaleista. Useita tekijöitä ja sairauksia voidaan yhdistää autonomisen hermoston epätasapainoon. Väitöskirjassa kehitettiin menetelmiä sydän- ja verisuonijärjestelmän autonomisen säätelyn kuvaamiseksi lyhytaikaisista kardiorespiratorisista tallenteista. Erityistä huomiota on kiinnitetty hengityksen vaikutukseen perinteisiin taajuustasosta laskettaviin muuttujiin, jotka kuvaavat autonomisen hermoston toimintaa. Väitöskirjan päätuloksia ja -tuotoksia ovat: 1) uusi adaptiiviseen suodatukseen pohjautuva laskennallinen menetelmä hengitysvaikutuksien poistamiseksi sydän- ja verisuonisignaaleista. Adaptiivinen suodatin vähensi matalan hengitystaajuuden aiheuttamaa vääristymää hermoston toimintaa kuvaavista parametreistä. Uusi menetelmä mahdollistaa kontrolloimattoman eli vapaan hengitystaajuus-protokollan käytön autonomisen hermoston toiminnan mittauksissa. 2) Uusia menetelmiä respiratorisen sinus arrytmian (RSA) määrittämiseksi sydän- ja verisuonisignaaleista. Kehitetyissä menetelmistä kahdessa käytetään adaptiivista suodatusta hyödyntäen joko mitattua hengityssignaalia tai EKG:stä johdettua hengityssignaalia. Kolmas menetelmä pohjautuu itsenäisten komponenttien analyysiin. Kehitetyt menetelmät RSA:n laskemiseksi sallivat hengitystaajuuden vaihtelun mittauksien aikana, mikä tekee ne fysiologisesti tarkemmaksi kuin perinteisesti käytetty korkeataajuinen (HF) komponentti, joka lasketaan taajuustasossa tietyltä kaistalta riippumatta hengitystaajuudesta. 3) Kehitettiin ja sovellettiin menetelmiä EKG:n ja verenpaineen matalataajuisten (LF) heilahtelujen tutkimista varten. Yhdessä tutkimuksessa sovellettiin aika-taajuustason esitystapaa vaihtelevan datan analysoimiksi. Kokeellinen tutkimus tehtiin aineistol, Notice Printed version has incorrect ISBN: 978-952-62-2312-4, it should be 978-952-62-2310-0., Huomautus Painetussa virheellinen ISBN: 978-952-62-2312-4, oikea 978-952-62-2310-0.